Pilot study of recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of chronic hepatitis B

Abstract

Recombinant human granulocyte-macrophage colony-stimulating factor is being used to improve the immunological function of patients with various diseases and to ameliorate hematological disorders. We investigated the tolerance and possible antiviral effect of the administration of daily doses of recombinant human granulocyte-macrophage colony-stimulating factor (3, 1 or 0.5 micrograms/kg body wt) to nine patients with chronic hepatitis B, alone or in combination with 5 MU interferon-alpha 2b. Recombinant human GM-CSF reduced significantly (p < 0.02) hepatitis B virus DNA levels. The three doses used were equally effective. Of the eight patients who completed the study, four became negative for HBV DNA and HBeAg; two of them seroconverted to HBe antibody. These four patients showed improvement in the histological activity of their liver disease. Ultimately, two patients regained normal ALT values. 2',5'-Oligoadenylate synthetase activity increased significantly (p < 0.01) in cell lysates of mononuclear cells cultured in vitro, coinciding with the reductions in hepatitis B virus DNA levels. Recombinant human granulocyte-macrophage colony-stimulating factor was well tolerated but produced a dose-dependent increase in white blood cell counts. It became intolerable at doses of 3 micrograms (and was reduced to 1.5 microgram); this effect was reversible after cessation of recombinant human granulocyte-macrophage colony-stimulating factor treatment. No remarkable variations occurred in other parameters. In conclusion, recombinant human granulocyte-macrophage colony-stimulating factor administration is safe and tolerable at doses of 0.5 to 1 microgram/kg body wt and may exert an antiviral effect in chronic hepatitis B.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokine-Mediated Immunopathogenesis of Hepatitis B Virus Infections

“…TGF-β1 treatment was able to effectively suppress HBV replication and the levels of viral transcripts, core protein, and nucleocapsid [32,138]; hence, TGF-β-based immunotherapy needs further exploration to achieve an optimal therapeutic regimen for HBV patients. Previous data have proposed that injection of granulocytemacrophage colony-stimulating factor (GM-CSF), known to be a good adjuvant for vaccination, before the vaccine might promote a stronger immune response in humans [139]; recombinant human GM-CSF significantly reduced hepatitis B virus DNA levels [140]. Subsequently, a pilot study demonstrated that a combined therapy of GM-CSF with a hepatitis B vaccine inhibited HBV replication in carrier children [141].…”

In Vivo and In Vitro Induction of MxA Protein in Peripheral Blood Mononuclear Cells from Patients Chronically Infected with Hepatitis C Virus

“…PBMC from controls and patients were isolated by Ficoll-Hypaque gradient sedimentation (SEROMED; Biochrom KG, Berlin, Germany) from fresh, heparinized venous blood, washed twice with PBS, and suspended in RPMI 1640 (Serva Feinbiochemica, Heidelberg, Germany) supplemented with 10% fetal bovine serum (Imperial Laboratories, Andover, UK), 20 mM HEPES, 2 mM glutamine, and antibiotics. To study MxA expression in vivo, 1 aliquot of freshly isolated PBMC was lysed immediately with lysis buffer, as previously described [20], and the cell extract was stored frozen until its use. Another aliquot of fresh PBMC from 29 of the 67 patients and 11 of the 21 healthy donors was cultured to analyze MxA responsiveness in vitro.…”

Immunopathogenesis and Immunotherapy for Viral Hepatitis

“…However, ALT levels were not elevated and viral load was not decreased. Cytokines Martin et al, 1993; Granulocyte macrophage-colony stimulating factor (GM-CSF) was safe and tolerable up to 1.0g/kg body wt, and induced HBV DNA negativity in 4/8 patients with chronic HBV infection. Wang et al, 2002; Combination therapy with GM-CSF (50g) and vaccine on the base of surface antigen (10g) (four intramuscular injections) significantly reduced serum HBV DNA in HBV carrier children.…”

“…In humans, GM-CSF (Martin et al, 1993, Wang et al, 2002 and IL-12 (Carreño et al, Zeuzem et al, 2001, Rigopoulou et al, 2005 have been used for treatment with some antiviral effects. They have been used as monotherapy or in combination with HB vaccine or lamivudine.…”